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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
`Silver Spring MD 20993
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`NDA APPROVAL
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`NDA 022511
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`Pozen
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`Attention: Paul A. Ossi
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`Senior Vice President, Regulatory Affairs
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`1414 Raleigh Road
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`Suite 400
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`Chapel Hill, N.C. 27517
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`Dear Mr. Ossi:
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`Please refer to your New Drug Application (NDA), received June 30, 2009, submitted under
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`section 505(b) of the Federal Food, Drug, and Cosmetic Act for Vimovo
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`(naproxen/esomeprazole magnesium) Delayed Release Tablets, 375 mg/20 mg and
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`500 mg/20 mg.
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`We acknowledge receipt of your submissions dated June 30, 2009; August 6, 2009;
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`October 29, 2009; November 11, 13, 19, and 30, 2009; December 18, 2009; March 4, 9, 24, 25,
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`and 26, 2010 and April 23, 28 and 30, 2010.
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`This new drug application provides for the use of Vimovo (naproxen/esomeprazole magnesium)
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`Delayed Release Tablets, 375 mg/20 mg and 500 mg/20 mg for relief of signs and symptoms of
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`osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, and to decrease the risk of
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`developing gastric ulcers in patients at risk of developing Non-Steroidal Anti-inflammatory Drug
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`(NSAID) associated gastric ulcers.
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`In our letter dated October 9, 2009, we notified you that a risk evaluation and mitigation strategy
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`(REMS) was required for Vimovo (naproxen/esomeprazole magnesium) to ensure that the
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`benefits of the drug outweigh the risks of cardiovascular and gastrointestinal adverse events. We
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`indicated that your REMS must include a Medication Guide and a timetable for submission of
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`assessments of the REMS.
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`After consultations between the Office of New Drugs and the Office of Surveillance and
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`Epidemiology, we have reconsidered the need for a REMS for this product. We believe that a
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`Medication Guide is necessary to inform patients of the serious risks of cardiovascular and
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`gastrointestinal adverse events. However, since other drugs currently approved in the non-
`steroidal anti-inflammatory drug (NSAID) class have Medication Guides with identical safety
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`information regarding these risks that are not included in a REMS, we will not require a REMS.
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`We have completed our review of this application, as amended. It is approved, effective on the
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`date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
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`NDA 022511
`Page 2
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indications in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`For the indication, relief of signs and symptoms of osteoarthritis (OA) and to decrease the risk of
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`developing gastric ulcers in OA patients at risk of developing NSAID-associated gastric ulcers,
`we are waiving the pediatric study requirement for ages birth to 16 years, 11 months. OA is one
`of the “adult-related” conditions that does not occur in pediatrics and qualifies for a waiver
`because studies would be impossible or highly impractical.
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`For the indication, relief of signs and symptoms of ankylosing spondylitis (AS) and to decrease
`the risk of developing gastric ulcers in AS patients at risk of developing NSAID-associated
`gastric ulcers, we are waiving the pediatric study requirement for ages birth to 16 years, 11
`months. Necessary studies are impossible or highly impracticable because there are too few
`pediatric patients with this disease to study. AS typically presents in young adulthood.
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`For the indication, relief of signs and symptoms of rheumatoid arthritis (RA) and to decrease the
`risk of developing gastric ulcers in RA patients at risk of developing NSAID-associated gastric
`ulcers, we are waiving the pediatric study requirement for ages birth to 1 year, 11 months.
`Necessary studies for pediatric patients in this age range are impossible or highly impracticable
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`because Juvenile Rheumatoid Arthritis (JRA) does not usually present at birth and fewer than 2%
`of all pediatric visits to a physician for an NSAID prescription for arthritis and arthropathy occur
`in this age group.
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`For the indication, relief of signs and symptoms of rheumatoid arthritis (RA) and to decrease the
`risk of developing gastric ulcers in RA patients at risk of developing NSAID-associated gastric
`ulcers, we are deferring submission of your pediatric studies for ages 2 to 16 years, 11 months
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`because this product is ready for approval for use in adults and the pediatric studies have not
`been completed.
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`NDA 022511
`Page 3
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`Your deferred pediatric studies required by section 505B(a) of the Federal Food, Drug, and
`Cosmetic Act are required postmarketing studies. The status of these postmarketing studies must
`be reported annually according to 21 CFR 314.81 and section 505B(a)(3)(B) of the Federal Food,
`Drug, and Cosmetic Act. These required studies are listed below.
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`1634-1 Deferred pediatric study under PREA in children 2 years to 11 years of age with
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`Juvenile Rheumatoid Arthritis (JRA)
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`A safety and population pharmacokinetic (PK) study in children with JRA who are 2 years to
`11 years, 11 months of age and require treatment with NSAIDs will be conducted. This study
`will be a 6 month, multicenter, open-label study to evaluate the dose, safety and PK of VIMOVO
`in this age group.
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`Final Report Submission: November 2014
`1634-2 Deferred pediatric study under PREA in children 12 years to 16 years and 11
`months of age with Juvenile Rheumatoid Arthritis (JRA)
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`A safety and population pharmacokinetic (PK) study in adolescents with JRA who are ages 12
`years to 16 years and 11 months and require treatment with NSAIDs will be conducted. This
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`study will be a 6 month, multicenter, open-label study to evaluate the safety and PK of VIMOVO
`in this age group.
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`Final Report Submission: October 2013
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`Submit final study reports to this NDA. For administrative purposes, all submissions related to
`these required pediatric postmarketing studies must be clearly designated “Required Pediatric
`Assessments”.
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`POSTMARKETING COMMITMENTS NOT SUBJECT TO THE REPORTING
`REQUIREMENTS UNDER SECTION 506B
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`We remind you of your postmarketing commitment in your submission dated March 4, 2010.
`This commitment is listed below.
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`1634-3 Within one year post-approval, you will transition from the naproxen dissolution test
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`currently in the NDA to the USP method that tests naproxen continuously, i.e. acid followed by
`buffer, using the same tablet.
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`July 2010
`Protocol Submission:
`Final Report Submission: April 2011
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`Submit study protocols to your IND 076301 for this product. Submit nonclinical and chemistry,
`manufacturing, and controls protocols and all study final reports to this NDA. In addition, under
`21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a status summary of each
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`NDA 022511
`Page 4
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`commitment in your annual report to this NDA. The status summary should include expected
`summary completion and final report submission dates, any changes in plans since the last
`annual report, and, for clinical studies/trials, number of patients entered into each study/trial. All
`submissions, including supplements, relating to these postmarketing commitments should be
`prominently labeled “Postmarketing Commitment Protocol,” “Postmarketing Commitment
`Final Report,” or “Postmarketing Commitment Correspondence.”
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit, via the FDA
`automated drug registration and listing system (eLIST), the content of labeling [21 CFR
`314.50(l)] in structured product labeling (SPL) format, as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm, that is
`identical to the enclosed labeling (text for the package insert, and Medication Guide).
`Information on submitting SPL files using eLIST may be found in the guidance for industry
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`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible via publicly available labeling repositories.
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and container labels that are identical to the carton and immediate
`container labels submitted on March 25, 2010 as soon as they are available, but no more than 30
`days after they are printed. Please submit these labels electronically according to the guidance
`for industry titled “Providing Regulatory Submissions in Electronic Format – Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
`(October 2005)”. Alternatively, you may submit 12 paper copies, with 6 of the copies
`individually mounted on heavy-weight paper or similar material. For administrative purposes,
`designate this submission “Final Printed Carton and Container Labels for approved NDA
`022511.” Approval of this submission by FDA is not required before the labeling is used.
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`Marketing the product with FPL that is not identical to the approved labeling text may render the
`product misbranded and an unapproved new drug.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
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`information about submission of promotional materials to the Division of Drug Marketing,
`Advertising, and Communications (DDMAC), see
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`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`Please submit one market package of the drug product when it is available.
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` METHODS VALIDATION
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`We have not completed validation of the regulatory methods. However, we expect your
`continued cooperation to resolve any problems that may be identified.
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` LETTERS TO HEALTH CARE PROFESSIONALS
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`If you issue a letter communicating important safety-related information about this drug product
`(i.e., a “Dear Health Care Professional” letter), we request that you submit an electronic copy of
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` the letter to both this NDA and to the following address:
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`NDA 022511
`Page 5
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`MedWatch
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`Food and Drug Administration
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`Suite 12B-05
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`5600 Fishers Lane
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`Rockville, MD 20857
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA (21
`CFR 314.80 and 314.81).
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`NDA 022511
`Page 6
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`If you have any questions, call Anna Simon, Regulatory Project Manager, at (301) 796-3509.
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`Enclosure: Package Insert with Medication Guide
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`Sincerely,
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` {See appended electronic signature page}
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`Donna Griebel, M.D.
`Director
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`Division of Gastroenterology Products
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
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`Application
`Type/Number
`--------------------
`NDA-22511
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`Submission
`Type/Number
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`ORIG-1
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`Submitter Name
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`Product Name
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`POZEN INC
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`------------------------------------------
`PN 400
`NAPROXEN/ESOMEPRAZOLE
`MAGNESIUM
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`DONNA J GRIEBEL
`04/30/2010
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